CREDENCE
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
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Overview
Canagliflozin reduced kidney failure and cardiovascular events in T2DM with albuminuric CKD.
Clinical takeaway
CREDENCE established SGLT2 inhibition as kidney-protective therapy for diabetic kidney disease, not simply glucose management.
Key result
Primary renal composite outcome was reduced by 30% (HR 0.70; 95% CI 0.59-0.82).
Practice impact
SGLT2 inhibitors became standard kidney-protective therapy in diabetic CKD with albuminuria when eGFR permits.
Evidence
Study design
Randomized, double-blind, placebo-controlled trial; stopped early for efficacy.
Enrollment
4,401
Follow-up
Median 2.62 years.
Geography
Multinational, 690 sites in 34 countries
Clinical question
Does canagliflozin improve renal and cardiovascular outcomes in T2DM with albuminuric CKD?
Population
- Patients with type 2 diabetes and albuminuric CKD (eGFR 30 to <90, urine albumin-to-creatinine ratio >300 to 5000 mg/g) on background RAAS blockade.
Intervention
Canagliflozin 100 mg daily.
Comparator
Placebo, both added to renin-angiotensin system blockade.
Primary outcome
Composite of ESKD, doubling of serum creatinine, or renal/CV death.
Canagliflozin reduced the primary composite of kidney failure and renal or cardiovascular death by 30% in diabetic kidney disease.
Hazard ratio / 0.7 / CI 95% CI 0.59-0.82 / p=<0.001
Key results
- Primary composite outcome: 43.2 vs 61.2 events per 1000 patient-years; HR 0.70; 95% CI 0.59-0.82; p=0.00001.
- End-stage kidney disease was reduced (HR 0.68; 95% CI 0.54-0.86).
- Cardiovascular death, MI, or stroke was reduced (HR 0.80; 95% CI 0.67-0.95).
- Hospitalization for heart failure was reduced (HR 0.61; 95% CI 0.47-0.80).
- There was no significant increase in amputation or fracture, unlike the earlier CANVAS program.
Harms
- SGLT2 inhibitors carry a risk of diabetic ketoacidosis and genital mycotic infection.
- Unlike the CANVAS program, CREDENCE did not show a significant increase in amputation or fracture.
Clinical Use
When to cite
- When discussing kidney-outcome evidence for SGLT2 inhibitors in albuminuric diabetic CKD.
Practice impact
- SGLT2 inhibitors became standard kidney-protective therapy in diabetic CKD with albuminuria when eGFR permits.
Applicability
- Most applicable to patients with type 2 diabetes and albuminuric CKD already on RAAS blockade.
Limitations
- Focused on diabetic albuminuric CKD; DAPA-CKD and EMPA-KIDNEY later extended benefit to nondiabetic and less albuminuric CKD.
- Enrolled patients with eGFR down to 30; less evidence at very low eGFR.
Common misinterpretations
- Do not restrict CREDENCE's message to glucose control; the kidney benefit is largely independent of glycemic effect.
- The amputation signal from CANVAS was not reproduced in CREDENCE and should not be assumed for all patients.
Citation
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. doi:10.1056/NEJMoa1811744
In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
- PMID
- 30990260